Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00446 (Sucralfate)
 278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sucralfate is a nonsystemic drug used in the therapy of peptic ulcer disease. It is an aluminum salt of a sulfated disaccharide which adheres to ulcerated sites and forms a cytoprotective barrier to acid peptic digestion. The purposes of this study were to determine whether sucralfate had antacid activity in humans and to test the validity of the in vitro antacid qualifying test by comparing its results for tableted products with those of in vivo studies. In the in vitro antacid qualifying test Maalox #1 (4 tablets) passes and sucralfate (1 gm.) failed. These findings were consistent with the results of in vivo tests utilizing a telemetric device, the Heidelberg capsule and tube aspirations. We conclude that sucralfate does not possess antacid properties and that the results of the standard in vitro antacid qualifying test correlated well with those of in vitro studies.
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PMID:In vitro and In vivo evaluations of a tableted antacid and sucralfate, a new antiulcer agent. 689 73

The safety of sucralfate, an aluminum salt of sucrose octasulfate that is used to treat peptic ulcer disease, is based on data from clinical trials in over 2,000 patients. In vitro, animal, and clinical studies have shown that sucralfate does not have anticoagulant effects, in contrast to other sulfated polysaccharides. Sucralfate was well tolerated by healthy volunteers in a multiple-dose study, in which the drug was administered in doses two and three times higher than the normal treatment dose, for 14 and 28 days, respectively. In open-label trials conducted in Japan, France, and Latin America in 1,600 subjects, side effects were reported in only 44 subjects, with the most common complaint being constipation (in 23 subjects). In the United States, safety evaluations of sucralfate were similar to those obtained in other countries, with only 12.9% of subjects treated with sucralfate (232) reporting side effects. The incidence of side effects in the placebo-treated group was about 12.1%. Furthermore, sucralfate has been shown to heal ulcers comparable to antacids and cimetidine. Its therapeutic efficacy, combined with the fact that it is well tolerated and free of serious systemic effects, enhances sucralfate's therapeutic clinical usefulness in the treatment of peptic ulcer disease.
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PMID:Sucralfate: a review of drug tolerance and safety. 703 54

Elevated aluminum concentrations have been implicated in several disease states in the elderly. We examined the effects of sucralfate, a basic aluminum salt of sucrose sulfate, and ranitidine, administered individually and in combination, on plasma and urine aluminum concentrations in the elderly in a prospective, randomized, three-arm crossover study. Subjects were 20 healthy volunteers over age 65 years, with no clinically significant comorbidities or recent use of aluminum-containing drugs or histamine (H)2-antagonists. The three regimens were ranitidine 300 mg at bedtime, sucralfate 1 g 4 times/day, and ranitidine 300 mg at bedtime plus sucralfate 1 g 4 times/day, administered for 4 weeks, with a washout period of at least 1 week between regimens. Plasma and urine aluminum concentrations were measured on days 0, 1, 7, 14, and 28 of each regimen. After 28 days, mean plasma aluminum concentrations were significantly higher in subjects receiving sucralfate alone (8.5 +/- 1.8 micrograms/L) and sucralfate plus ranitidine (5.1 +/- 1.3 micrograms/L) compared with those receiving ranitidine alone (2.4 +/- 0.7 micrograms/L). Urine aluminum concentrations were significantly higher in subjects receiving sucralfate alone (133.2 +/- 32.8 micrograms/g creatinine) and sucralfate plus ranitidine (148.1 +/- 51.9 micrograms/g creatinine) compared with those receiving ranitidine alone (11.0 +/- 3.7 micrograms/g creatinine). There was no significant difference in plasma or urine aluminum concentrations between subjects who received sucralfate alone versus those who received sucralfate plus ranitidine. Sucralfate 4 g/day in elderly subjects produces a significant increase in both plasma and urine aluminum concentrations, compared with ranitidine 300 mg/day. This increase most likely is secondary to gastrointestinal absorption of aluminum in the sucralfate formulation. The clinical relevance of this increase requires further evaluation.
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PMID:Effects of sucralfate and ranitidine on aluminum concentrations in elderly volunteers. 860 82

Metal cations such as aluminum, magnesium, ferrous sulfate, and zinc are thought to form chelation complexes with fluoroquinolone antibiotics and prevent the drugs from being absorbed. Sucralfate, which has a high aluminum content, reduces the bioavailability of ciprofloxacin to approximately 4%. The concomitant administration of ciprofloxacin and sucralfate resulted in treatment failure for a patient with prostatitis and a subsequent 5-day hospitalization. Fluoroquinolone antibiotics should be administered at least 2 hours before agents containing metal cations to allow for their absorption. In addition, sucralfate should not be administered less than 6 hours before fluoroquinolone antibiotic administration.
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PMID:Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction. 882 Apr 79

Sucralfate inhibits activity of certain Helicobacter pylori enzymes, implying that this medication may limit gastric cell injury associated with H pylori infection. This study evaluates the ability of sucralfate and its two major structural components, sucrose octasulfate and aluminum hydroxide, to reduce the cytotoxic effects of H pylori and to inhibit binding of H pylori to human gastric epithelial cells. Experiments were performed using human gastric epithelial cells isolated from gastric biopsy tissue taken at upper gastrointestinal endoscopy. Primary cultures of human gastric epithelial cells, when exposed to broth-culture supernatant from a vacuolating cytotoxin-positive H pylori strain, were shown to form cytoplasmic vacuoles. Preexposing H pylori brothculture supernatant to sucralfate reduced vacuole formation in human gastric epithelial cells; however, preexposure of H pylori broth-culture supernatant to aluminum hydroxide or sucrose octasulfate did not reduce vacuolation in human gastric epithelial cells. H pylori binding to human gastric epithelial cells was significantly reduced when H pylori was exposed to sucralfate prior to incubating the bacterium with human gastric epithelial cells. These data show that sucralfate, but not its two major components, reduces the toxicity of an H pylori-produced cytotoxin (VacA) and decreases H pylori adherence to human gastric epithelial cells. This reduction in H pylori cytotoxicity may contribute to sucralfate's ulcerhealing properties and to the lower ulcer recurrence rates seen in patients treated with this medication.
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PMID:Effects of sucralfate on vacuolating cytotoxin activity and adherence of Helicobacter pylori to human gastric epithelial cells. 893 34

We have established models of cell damage induced by acid and pepsin using rat gastric epithelial cells (RGM1). In the present study, the effects of aluminum hydroxide [Al(OH)3] and potassium sucrose octasulfate (KSOS), which are components of sucralfate, and sucralfate on cell damage and peptic activity of pepsin were examined. Pretreatment of cells with sucralfate (0.1-3 mg/ml) or Al(OH)3 (0.1-1 mg/ml) for 2 hr prevented both acid- (pH 4.0) and pepsin- (pH 4.5) induced cell damage. However, KSOS (0.1-1 mg/ml) did not show any effects on two different types of cell damage. The peptic activity of pepsin at pH 4.5 was about 10% of that at pH 2.0. Sucralfate and KSOS slightly inhibited peptic activity at pH 4.5. Al(OH)3 inhibited peptic activity by approximately 50%; however, no concentration-dependent pattern was observed. Pepstatin (0.003-0.1 mg/ml), a specific inhibitor of pepsin, inhibited the peptic activity in a concentration-dependent manner. Here, we confirmed that sucralfate and Al(OH)3 have cytoprotective effects against acid- and pepsin-induced cell damage. The mechanism behind the cytoprotective effects of sucralfate seems to relate to adhesion of the cell surface and neutralization of hydrogen ion by aluminum that prevents the penetration of hydrogen ions into the cells.
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PMID:Effects of sucralfate and its components on acid- and pepsin-induced damage to rat gastric epithelial cells. 933 82

BACKGROUND: Sucralfate, used in stress ulcer prophylaxis, contains aluminum, which can be absorbed from the gut. OBJECTIVE: To determine whether toxic serum aluminum levels can develop after short-term sucralfate therapy in critically ill children. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care unit of a pediatric university hospital. PATIENTS: Nineteen patients receiving mechanical ventilatory support (median age, 5 yrs [range, 0.25-16 yrs]; median weight, 17 kg [range, 3.5-60 kg]). INTERVENTIONS: All patients received sucralfate suspension nasogastrically. Measurements and RESULTS: Serum aluminum concentrations were measured after a short period on sucralfate therapy (median time, 7 days [range, 3-14 days]). There was no correlation between total sucralfate dose received (p =.35) or dose of sucralfate per unit of body weight (p =.55) and serum aluminum. Nine patients received peritoneal dialysis. Serum aluminum levels were higher in the nine patients who received peritoneal dialysis (median aluminum concentration, 2.86 &mgr;mol/L [range, 0.19-12.3 &mgr;mol/L]) than the ten patients not dialyzed (median aluminum concentration, 0.55 &mgr;mol/L [range, 0.18-0.94 &mgr;mol/L]) (p =.001). The peak serum creatinine levels were higher in the dialyzed patients (median creatinine level, 500 &mgr;mol/L [range, 163-910 &mgr;mol/L]) than those not dialyzed (median creatinine level, 98 &mgr;mol/L [range, 36-415 &mgr;mol/L]) (p =.006). There was a trend toward correlation between peak serum creatinine and serum aluminum (p =.06). CONCLUSION: Aluminum accumulation occurs in children with acute renal failure on sucralfate, especially those receiving dialysis. If sucralfate is used in children in renal failure, serum aluminum concentrations should be monitored regularly.
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PMID:Aluminum accumulation in critically ill children on sucralfate therapy. 1279 50

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.
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PMID:Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice. 1556 29


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